Modified release niacin pharmaceutical formulations

Abstract

Pharmaceutical formulations comprising niacin in a matrix comprising a hydrophobic polymer that modifies release of niacin.

1 . A pharmaceutical formulation comprising niacin in a matrix that modifies release of niacin by incorporating a hydrophobic material, the formulation providing, following administration to a healthy human, at least one of the pharmacokinetic parameters C max  and AUC 0-∞  greater than a corresponding value obtained from administering a pharmaceutical formulation containing a similar or greater amount of niacin in a matrix that modifies release of niacin by incorporating a hydrophilic polymer. 
     
     
         2 . The pharmaceutical formulation of  claim 1 , wherein at least one of the pharmacokinetic parameters C max  and AUC 0-∞  is greater than a corresponding value obtained from administering a pharmaceutical formulation containing at least about 25 percent more niacin in a matrix that modifies release of niacin by incorporating a hydrophilic polymer. 
     
     
         3 . The pharmaceutical formulation of  claim 1 , wherein at least one of the pharmacokinetic parameters C max  and AUC 0-∞  is greater than a corresponding value obtained from administering a pharmaceutical formulation containing at least about 35 percent more niacin in a matrix that modifies release of niacin by incorporating a hydrophilic polymer. 
     
     
         4 . The pharmaceutical formulation of  claim 1 , wherein a hydrophobic material comprises a hydrophobic polymer. 
     
     
         5 . The pharmaceutical formulation of  claim 1 , wherein a hydrophobic material comprises a hydrophobic polymer comprising a copolymer of an alkyl acrylate and an alkyl methacrylate, alkyl groups being the same or different and having 1 to about 4 carbon atoms. 
     
     
         6 . The pharmaceutical formulation of  claim 1 , wherein a hydrophobic material comprises a hydrophobic polymer comprising a 1:1 copolymer of ethyl acrylate and methyl methacrylate, having an average molecular weight about 600,000. 
     
     
         7 . The pharmaceutical formulation of  claim 1 , wherein a matrix is formed by a method comprising granulating a solid mixture comprising niacin with a liquid comprising a hydrophobic polymer. 
     
     
         8 . The pharmaceutical formulation of  claim 1 , wherein a matrix is formed by a method comprising granulating a particulate mixture comprising niacin with an aqueous suspension comprising a hydrophobic polymer. 
     
     
         9 . The pharmaceutical formulation of  claim 1 , wherein a matrix is formed by a method comprising combining a particulate mixture comprising niacin with a hydrophobic polymer. 
     
     
         10 . The pharmaceutical formulation of  claim 1 , wherein a hydrophobic material comprises a fatty substance or a mineral. 
     
     
         11 . The pharmaceutical formulation of  claim 1 , having a first polymer coating disposed over a tablet formed using a matrix comprising a hydrophobic polymer. 
     
     
         12 . The pharmaceutical formulation of  claim 1 , having a first polymer coating comprising a cellulose derivative, disposed over a tablet formed using a matrix comprising a hydrophobic polymer. 
     
     
         13 . The pharmaceutical formulation of  claim 1 , having a first polymer coating comprising a hydroxypropyl methylcellulose, disposed over a tablet formed using a matrix comprising a hydrophobic polymer. 
     
     
         14 . The pharmaceutical formulation of  claim 11 , having a coating of an enteric polymer disposed over a first polymer coating. 
     
     
         15 . The pharmaceutical formulation of  claim 11 , having a coating of a copolymer of methacrylic acid, or an alkyl methacrylate, and an alkyl acrylate, disposed over a first polymer coating. 
     
     
         16 . The pharmaceutical formulation of  claim 11 , having a coating of a hydroxypropyl methylcellulose phthalate disposed over a first polymer coating. 
     
     
         17 . A pharmaceutical formulation comprising niacin in a matrix that modifies release of niacin by incorporating a hydrophobic material, and a first polymer coating disposed over a tablet formed using the matrix, the formulation providing, following administration to a healthy human, at least one of the pharmacokinetic parameters C max  and AUC 0-∞  greater than a corresponding value obtained from administering a pharmaceutical formulation containing a similar or greater amount of niacin in a matrix that modifies release of niacin by incorporating a hydrophilic polymer. 
     
     
         18 . The pharmaceutical formulation of  claim 17 , wherein at least one of the pharmacokinetic parameters C max  and AUC 0-∞  is greater than a corresponding value obtained from administering a pharmaceutical formulation containing at least about 25 percent more niacin in a matrix that modifies release of niacin by incorporating a hydrophilic polymer. 
     
     
         19 . The pharmaceutical formulation of  claim 17 , wherein a hydrophobic material comprises a copolymer of an alkyl acrylate and an alkyl methacrylate, alkyl groups being the same or different and having 1 to about 4 carbon atoms. 
     
     
         20 . The pharmaceutical formulation of  claim 17 , wherein a hydrophobic material comprises a 1:1 copolymer of ethyl acrylate and methyl methacrylate, having an average molecular weight about 600,000. 
     
     
         21 . The pharmaceutical formulation of  claim 17 , wherein a first polymer coating comprises a cellulose derivative. 
     
     
         22 . The pharmaceutical formulation of  claim 17 , wherein a first polymer coating comprises a hydroxypropyl methylcellulose. 
     
     
         23 . The pharmaceutical formulation of  claim 17 , having a coating of an enteric polymer disposed over a first polymer coating.